In industrialized societies increases in arterial stiffness and left ventricular (LV) mass are considered part of normative aging. However, considerable heterogeneity exists in the age-associated changes in these variables both across cultures as well as within a given population. The ultimate goals of this project are to determine how alterations in arterial stiffness affect the myocardium and whether in outcome studies they relate to vascular insufficiency syndromes, e.g., stroke or myocardial infarction. We have initiated a pilot study in which measurements of cardiac mass (via NMR), filling properties and isovolumic relaxation time (via Doppler echocardiography), carotid pressure pulse (via applanation tomography) and arterial pulse wave velocity (Doppler sonography) are made in BLSA men and women who differ with respect to age, race, arterial pressure, body composition, and physical conditioning status. Results indicate that arterial stiffness as reflected by pulse wave velocity, increases with age, whereas stiffness varies inversely with exercise capacity. Further-more, i highly physically conditioned older individuals (>60 yrs of age) the arterial stiffness indices are markedly reduced relative to their sedentary age peers and resemble those of younger individuals, although the age- associated increase in systolic pressure persists. We have undertaken an initiative to extend many of these studies to Black Americans and to non- Western populations in which different patterns of arterial pressure change occurs with aging (in China via a research contract (cf. #N01-AG-02-2118)). Long term goals include determination of whether "normative"age-associated changes in cardiac structure (i.e. increasing LV mass) and function (delaye LV relaxation and reduced early diastolic filling rates) are directly related to changes in arterial stiffness. If such is the case, a long-term intervention trial might be justified to see whether amelioration of arterial stiffness by medication or lifestyle intervention can attenuate these age-associated changes in cardiac structure and function and reduce future cardiovascular morbidity. Preliminary data indicate direct correlations between echocardiographic LV mass and arterial stiffness in BLSA volunteers. Finally, we have initiated a trial to determine whether acute reduction of afterload with sodium nitroprusside can attenuate aging changes in arterial stiffness and improve cardiac performance in older subjects during maximal bicycle exercise.